A Second-Generation Tandem Ring-Closing Metathesis Cleavable Linker for Solid-Phase Oligosaccharide Synthesis

A tandem ring-closing metathesis cleavable linker system for solid-phase oligosaccharide synthesis has been developed. The acid- and base-stable linker can be readily cleaved with Grubbs second-generation catalyst without the use of alkene additives to liberate the assembled oligosaccharides from the solid support. Application of the linker was shown in three solid-phase oligosaccharide synthesis campaigns. Two frame-shifted hyaluronic acid fragments were prepared, and we also report the synthesis of a trimeric β-1,3-glucan fragment, in which, next to the linker, our recently reported 4-azido-2,2-dimethylbutanoyl (AzDMB) protective group was applied.

[1]  Peter H Seeberger,et al.  Automated polysaccharide synthesis: assembly of a 30mer mannoside. , 2013, Angewandte Chemie.

[2]  P. Seeberger,et al.  Automated solid-phase synthesis of chondroitin sulfate glycosaminoglycans. , 2013, Angewandte Chemie.

[3]  P. Seeberger,et al.  Automated solid phase synthesis of oligoarabinofuranosides. , 2013, Chemical communications.

[4]  H. Overkleeft,et al.  2,2-Dimethyl-4-(4-methoxy-phenoxy) butanoate and 2,2-dimethyl-4-azido butanoate: two new pivaloate-ester-like protecting groups. , 2013, Organic letters.

[5]  P. Seeberger,et al.  Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker , 2013, Beilstein journal of organic chemistry.

[6]  H. Overkleeft,et al.  Automated solid-phase synthesis of hyaluronan oligosaccharides. , 2012, Organic letters.

[7]  Chi-Huey Wong,et al.  Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese , 2011 .

[8]  N. Reichardt,et al.  A new linker for solid-phase synthesis of heparan sulfate precursors by sequential assembly of monosaccharide building blocks. , 2011, Chemical communications.

[9]  Biao Yu,et al.  Glycosylation with glycosyl N-phenyltrifluoroacetimidates (PTFAI) and a perspective of the future development of new glycosylation methods. , 2010, Chemical communications.

[10]  G. Boons,et al.  Chiral auxiliary mediated 1,2-cis glycosylations for the solid supported synthesis of a biologically important branched α-glucan , 2010, Nature chemistry.

[11]  A. Demchenko,et al.  Mechanism of chemical O-glycosylation: from early studies to recent discoveries. , 2010, Organic & biomolecular chemistry.

[12]  Katsunori Tanaka,et al.  Synthesis of a sialic acid containing complex-type N-glycan on a solid support. , 2009, Chemistry, an Asian journal.

[13]  J. Mague,et al.  Synthesis of the beta-1,3-glucan, laminarahexaose: NMR and conformational studies. , 2009, Carbohydrate research.

[14]  R. R. Schmidt,et al.  Neue Prinzipien für die Bildung von glycosidischen Bindungen , 2009 .

[15]  Peter H Seeberger,et al.  Automated carbohydrate synthesis as platform to address fundamental aspects of glycobiology--current status and future challenges. , 2008, Carbohydrate research.

[16]  T. Nokami,et al.  Electrochemical generation of glycosyl triflate pools. , 2007, Journal of the American Chemical Society.

[17]  C. Reese,et al.  Oligo- and poly-nucleotides: 50 years of chemical synthesis. , 2005, Organic & biomolecular chemistry.

[18]  Sarah J Kodumal,et al.  Total synthesis of long DNA sequences: synthesis of a contiguous 32-kb polyketide synthase gene cluster. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Yukishige Ito,et al.  On-resin real-time reaction monitoring of solid-phase oligosaccharide synthesis. , 2002, Journal of the American Chemical Society.

[20]  Biao Yu,et al.  Glycosyl trifluoroacetimidates. Part 1: Preparation and application as new glycosyl donors , 2001 .

[21]  R. Schmidt,et al.  A new phenoxyacetate-based linker system for the solid-phase synthesis of oligosaccharides. , 2001, Organic letters.

[22]  Peter H. Seeberger,et al.  Automated Solid-Phase Synthesis of Oligosaccharides , 2001, Science.

[23]  A. Albeck,et al.  Efficient and Stereospecific Synthesis of (z)-Hex-3-Enedioic Acid, a Key Intermediate for Gly-Gly cis Olefin Isostere , 2000 .

[24]  P. Seeberger,et al.  Solid-phase oligosaccharide synthesis and combinatorial carbohydrate libraries. , 2000, Chemical reviews.

[25]  R. Schmidt,et al.  Solid‐Phase Synthesis of a Branched Hexasaccharide Related to Lacto‐N‐Hexaose , 2000 .

[26]  R. Schmidt,et al.  APPLICATION OF A RING CLOSING METATHESIS BASED LINKER TO THE SOLID PHASE SYNTHESIS OF OLIGOSACCHARIDES , 1999 .

[27]  P. Seeberger,et al.  Solid-phase oligosaccharide synthesis: preparation of complex structures using a novel linker and different glycosylating agents. , 1999, Organic letters.

[28]  S. Balasubramanian,et al.  Solid phase synthesis - designer linkers for combinatorial chemistry : a review , 1999 .

[29]  Stefaan De Smedt,et al.  HYALURONAN : PREPARATION, STRUCTURE, PROPERTIES, AND APPLICATIONS , 1998 .

[30]  Dirk Weigelt,et al.  A linker for solid phase carbohydrate synthesis, permitting the introduction of variable anomeric functionality in the release step , 1998 .

[31]  Yukishige Ito,et al.  Solid phase synthesis of polylactosamine oligosaccharide , 1996 .

[32]  S. Kent.  Chemical synthesis of peptides and proteins. , 1988, Annual review of biochemistry.

[33]  R. Letsinger,et al.  Stepwise synthesis of oligodeoxyribonucleotides on an insoluble polymer support. , 1966, Journal of the American Chemical Society.

[34]  James N. BeMiller,et al.  (1→3)-β-d-Glucans as biological response modifiers: a review of structure-functional activity relationships , 1995 .